ArticleJournal of translational medicine2025
Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Uniform shear-induced platelet aggregation analysis via microfluidics fabricated from 3D-printed mold: a rapid platform for antiplatelet drug assessment.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2026Article
- The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling-A Review Article.Biomedicines · 2026Review
- Clonal Hematopoiesis (CHIP) in Pulmonary Embolism and CTEPH: Evidence, Mechanisms, and Risk Stratification.International journal of molecular sciences · 2026Review
- Neutrophil Extracellular Traps in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Targets.Journal of inflammation research · 2026Review
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24 authors.
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Abstract
backgroundUndissolved thrombus blocks the pulmonary arteries in chronic thromboembolic pulmonary hypertension (CTEPH), a potentially fatal illness that raises pulmonary resistance, causes right heart failure, and even results in death. Although platelets are linked to vascular dysfunction and thrombus formation, it is yet unknown what precise proteome alterations and mechanistic roles they play in CTEPH.
methodsWe extracted platelet-rich plasma from peripheral blood and separated the plasma to obtain enriched platelet pellet (EPP). Quantitative proteomics was used to examine EPP from CTEPH patients and healthy controls using mass spectrometry. The relationship between protein levels and clinical markers of right heart function was examined. Platelet activity, morphology, and interactions with other blood components were evaluated using transmission electron microscopy, immunofluorescence, and flow cytometry.
resultsThe proteomic investigation found that 179 proteins were differentially expressed in CTEPH patients. The analysis revealed that these proteins were involved in crucial processes such as complement and coagulation cascades, phagosome, and neutrophil extracellular trap (NET) formation. Elevated proteins, specifically NOX2, PAD4, ITGB2, and HMGB1, have been associated to platelet-neutrophil aggregates and NET formation. In addition, enhanced P-selectin expression in platelets and plasma confirmed greater platelet activation in CTEPH patients. Notably, PAD4 and NOX2 levels showed a substantial correlation with hemodynamic parameters and right heart dysfunction. MPO-DNA, a NET marker associated with P-selectin and ITGB2 expression, was discovered in higher concentrations in CTEPH patients' plasmas.
conclusionPlatelet aggregation and activation in CTEPH encourage the formation of NETs, which advances the disease and prolongs thrombus. Right heart insufficiency and hemodynamic markers had a strong correlation with PAD4 and NOX2 levels, indicating that these biomarkers may be employed to assess the severity and prognosis of CTEPH disease and offer a fresh approach to targeted treatment. The results highlight the need for additional study to elucidate platelet-mediated pathways and create therapies for CTEPH that target platelets.
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